1. Field of Invention
The invention generally relates to a strategy or method of preventing, arresting, reversing and treatment of atherosclerosis. The invention, in particular, suggests that enhancing the activities of Δ6 and Δ5 desaturases such that the cell, tissue, and plasma levels of various polyunsaturated fatty acids (PUFAs) and, in particular that of endothelial cells lining the blood vessels will increase and this leads to arrest or prevention of atherosclerosis. The enhanced activities of Δ6 and Δ5 desaturases and various PUFAs will lead to increased production of their products such as prostacyclin (PGI2), PGI3, lipoxins, resolvins, protectins, PGE1 (prostaglandin E1) such that atherosclerotic process will be prevented, arrested, reversed and this will lead to efficient treatment of even established atherosclerosis and its associated conditions such as obesity, type 2 diabetes mellitus, coronary heart disease (CHD), hypertension, and metabolic syndrome X, and depression, and Alzheimer's disease. More particularly, the invention is directed to the efficacious use of proteins, peptides, lipids, lipoproteins, glycolipids, synthetic chemicals such as statins and their derivatives, troglitazones and their derivatives, cDNA clones of Δ6 and Δ5 desaturases, genes of Δ6 and Δ5 desaturases, for the prevention, arrest, reversal and treatment of atherosclerosis. It is suggested that decreased or defective either qualitative or quantitative activity of Δ6 and Δ5 desaturases is responsible for atherosclerosis. Furthermore, the invention also teaches that appropriate and desired amount of activation of Δ6 and Δ5 desaturases would occur leading to the synthesis, formation and accumulation of various polyunsaturated fatty acids and the synthesis, formation and release of their products such as prostacyclin (PGI2), PGI3, lipoxins, resolvins, protectins, PGE1 (prostaglandin E1), and nitric oxide (NO) would occur leading to the prevention, arrest, reversal and treatment of atherosclerosis. This invention also teaches efficient use of methods to enhance the activity of Δ6 and Δ5 desaturases specifically in the cerebral blood vessels by various synthetic and natural compounds which are able to cross blood brain barrier (BBB) when administered orally, parentarally or by any other route and enter brain in sufficient quantities to produce their desired actions.
2. Description of the Related Art
Atherosclerosis, the major underlying cause for coronary heart disease (CHD), is a dynamic process. In majority of the instances, hyperlipidemia, diabetes mellitus, hypertension, and obesity are the main risk factors for the development of atherosclerosis and CHD. Several studies revealed that in CHD, hypertension, diabetes mellitus, hyperlipidemias, and obesity, EFA (essential fatty acids) metabolism is abnormal such that plasma and tissue concentrations of γ-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in the phospholipid fraction are low (1-8). Increased intake of polyunsaturated fatty acids (PUFAs especially in the form of GLA, DGLA, EPA and DHA) protects against the development of these diseases both in experimental animals (9-12) and humans (13), though the exact mechanism of this protective action is unclear. GLA, DGLA, AA, EPA, and DHA form precursors to prostaglandin E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, neuroprotectin D1 (NPD1), enhance NO generation, and interact with NO to form nitrolipids that have anti-inflammatory actions, prevent platelet aggregation, inhibit leukocyte activation and augment wound healing and resolve inflammation that may account for their beneficial actions. This implies that an altered EFA metabolism in the form of a block in the activity of Δ6 and Δ5 desaturases, which are essential for the formation of long-chain metabolites from dietary linoleic acid (LA, 18:2 ω-6) and α-linolenic acid (ALA, 18:3 ω-3), could lead to reduced formation of PGE1, PGI2, NO, LXs, resolvins, and nitrolipids that could initiate and aggravate atherosclerosis.